Clefting
Gene: PLCB4
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 1 Feb 2023, 5:13 p.m. | Last Modified: 1 Feb 2023, 5:13 p.m.
Panel Version: 3.5
PMID: 28328130 - Romanelli-Tavares et al 2017 - report 2 patients (1 sporadic, 1 familial) with previous published phenotypic descriptions of Auriculocondylar syndrome in which heterozygous missense variants were found in PLCB4 after sequencing PLCB4, GNAI3,and EDN1. Cleft palate was noted in 2/7 members of the familial case.
This is a 3rd case in which cleft palate is reported in association with PLCB4 variants and therefore there is sufficient evidence to promote this gene to green following GMS review.Created: 25 May 2022, 11:16 a.m. | Last Modified: 25 May 2022, 11:16 a.m.
Panel Version: 2.68
Comment on list classification: Promoting this gene from red to amber as there are two cases of auriculocondylar syndrome 2 associated with variants in this gene where cleft palate is part of the phenotype.Created: 20 Jul 2021, 5:55 p.m. | Last Modified: 20 Jul 2021, 5:55 p.m.
Panel Version: 2.34
Associated with Auriculocondylar syndrome 2 #614669 (AD, AR) in OMIM with Cleft palate as a clinical feature.
Summary: 3 cases of Auriculocondylar syndrome reported with homozygous/compound het variants or deletions in PLCB4 and 12 cases with heterozygous variants in PLCB4. Only 2/12 cases reported with cleft palate as part of the phenotype, although a literature review by Storm et al 2005 (PMID: 16114046) suggests that palate abnormalities are found in 62.5% of Auriculocondylar syndrome cases in general.
PMID: 32201334 - Nabil et al 2020 - report a multigenerational Egyptian kindred with high intrafamilial variability in Auriculocondylar syndrome in which a heterozygous missense variant in PLCB4 was identified by WES. Cleft palate not reported.
PMID: 27007857 - Leoni et al 2016 - report a child with a ACS phenotype in addition to gastrointestinal dysfunction and severe sleep-related breathing abnormalities and a homozygous frameshift mutation in PLCB4. Cleft palate not reported.
PMID: 23913798 - Kido et al 2013 - describe two brothers with ACS plus central apnea and macropenis in which compound heterozygous splice site mutations in PLCB4 were identified. Each parent harboured one of the mutations. Cleft palate not reported.
PMID: 22560091 - Rieder et al 2012 - describe 5 cases in which missense variants in PLCB4 were found (1 de novo, 4 familial but 2 with incomplete penetrance). The proband in family M003 is reported to have cleft palate.
PMID: 23315542 - Gordon et al 2013 - report 6 cases with heterozygous PLCB4 missense variants, and 1 case with a homozygous PLCB4 intragenic deletion (heterozygous parents unaffected). Cleft palate (as part of Pierre Robin sequence) is only reported in 1/7 cases (case 3 - detailed phenotype in described as case 2 in Greig et al (PMID: 22286465). They suggest they missense variants are acting in a dominant negative mode.Created: 20 Jul 2021, 4:43 p.m. | Last Modified: 20 Jul 2021, 4:43 p.m.
Panel Version: 2.33
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Auriculocondylar syndrome 2, OMIM:614669; auriculocondylar syndrome 2, MONDO:0013845
Publications
Cleft palate is a feature of this craniofacial disorder.Created: 29 Jan 2021, 3:55 a.m. | Last Modified: 29 Jan 2021, 3:55 a.m.
Panel Version: 2.20
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Auriculocondylar syndrome 2, MIM# 614669
Publications
Tag Q2_22_rating was removed from gene: PLCB4.
Source NHS GMS was added to PLCB4. Source Expert Review Green was added to PLCB4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q2_22_rating tag was added to gene: PLCB4.
Publications for gene: PLCB4 were set to 16114046; 32201334; 27007857; 23913798; 2560091; 23315542
Phenotypes for gene: PLCB4 were changed from Cleft palate to Auriculocondylar syndrome 2, OMIM:614669; auriculocondylar syndrome 2, MONDO:0013845
Publications for gene: PLCB4 were set to
Mode of inheritance for gene: PLCB4 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Gene: plcb4 has been classified as Amber List (Moderate Evidence).
PLCB4 was added to Clefting panel. Sources: Victorian Clinical Genetics Services
PLCB4 was created by Ellen McDonagh